Document Type : Original Article(s)

Authors

1 Isfahan Pharmaceutical Sciences Research Center AND Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

3 Professor, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

4 Professor, Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

5 Department of Psychiatry and Neuroscience, Laval University, Quebec, QC, Canada

6 Associate Professor, Isfahan Pharmaceutical Sciences Research Center AND Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

BACKGROUND: This study examined the relationship between serum glutathione peroxidase 1 (GPx-1) activity and endothelial dysfunction in the subjects with and without metabolic syndrome (MetS).METHODS: This case-control study was conducted on 76 subjects, 38 were patients with MetS and 38 were without MetS. The demographic, clinical, and laboratory features of the subjects were measured and then compared. The MetS was diagnosed according to the definitions of the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF). Serum GPx-1 activity was measured by standard methods. Endothelial dysfunction was assessed with flow-mediated dilation (FMD) technique.RESULTS: In case-control study of 76 subjects, all of MetS risk factors including abdominal obesity, triglyceride (TG), low serum level of high-density lipoprotein cholesterol (HDL-C), hypertension (HTN), and fasting plasma glucose (FPG) were significantly higher than healthy individuals (P < 0.050). FMD was significantly lower than normal subjects (P < 0.050). Serum GP-1 activity was significantly lower in patients with MetS compared to normal subjects (21.7 ± 13.5 vs. 79.0 ± 38.6, respectively) (P = 0.001). The value of GPx-1 was significantly correlated with diastolic blood pressure (DBP) (r = -0.249, P = 0.040), C-reactive protein (CRP) (r = -0.409, P = 0.014), and FMD (r = 0.293, P = 0.050) in patients with MetS. The results of logistic regression showed that a unite increase in CRP (mg/dl), FMD (%), and endothelin-1 (ET-1) (pg/ml) and a unit decrease in GPx significantly increased the odds ratio (OR) of MetS; after adjusting for age and sex the results remained significant except for FMD (P < 0.050)CONCLUSION: Endothelial dysfunction is related to serum GPx-1 activity in patients with MetS. GPX-1 activity is associated with risk of cardiovascular diseases (CVDs) and peripheral vascular diseases (PVDs) in patients with MetS.

Keywords

  1. Vavrova L, Kodydkova J, Zeman M, Dusejovska M, Macasek J, Stankova B, et al. Altered activities of antioxidant enzymes in patients with metabolic syndrome. Obes Facts 2013; 6(1): 39-47.
  2. Karaman A, Aydin H, Geckinli B, Cetinkaya A, Karaman S. DNA damage is increased in lymphocytes of patients with metabolic syndrome. Mutat Res Genet Toxicol Environ Mutagen 2015; 782: 30-5.
  3. Yubero-Serrano EM, Delgado-Lista J, Pena-Orihuela P, Perez-Martinez P, Fuentes F, Marin C, et al. Oxidative stress is associated with the number of components of metabolic syndrome: LIPGENE study. Exp Mol Med 2013; 45: e28.
  4. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289(1): 76-9.
  5. Baez-Duarte BG, Zamora-Ginez I, De Jesus KL, Torres-Rasgado E, Gonzalez-Mejia ME, Porchia L, et al. Association of the metabolic syndrome with antioxidant defense and outstanding superoxide dismutase activity in Mexican subjects. Metab Syndr Relat Disord 2016; 14(3): 154-60.
  6. Baez-Duarte BG, Mendoza-Carrera F, Garcia-Zapien A, Flores-Martinez SE, Sanchez-Corona J, Zamora-Ginez I, et al. Glutathione peroxidase 3 serum levels and GPX3 gene polymorphisms in subjects with metabolic syndrome. Arch Med Res 2014; 45(5): 375-82.
  7. Pena-Orihuela P, Camargo A, Rangel-Zuniga OA, Perez-Martinez P, Cruz-Teno C, Delgado-Lista J, et al. Antioxidant system response is modified by dietary fat in adipose tissue of metabolic syndrome patients. J Nutr Biochem 2013; 24(10): 1717-23.
  8. Anagnostis P, Efstathiadou ZA, Gougoura S, Polyzos SA, Karathanasi E, Dritsa P, et al. Oxidative stress and reduced antioxidative status, along with endothelial dysfunction in acromegaly. Horm Metab Res 2013; 45(4): 314-8.
  9. Beckett GJ, Arthur JR. Selenium and endocrine systems. J Endocrinol 2005; 184(3): 455-65.
  10. Forgione MA, Weiss N, Heydrick S, Cap A, Klings ES, Bierl C, et al. Cellular glutathione peroxidase deficiency and endothelial dysfunction. Am J Physiol Heart Circ Physiol 2002; 282(4): H1255-H1261.
  11. Fernandez-Sanchez A, Madrigal-Santillan E, Bautista M, Esquivel-Soto J, Morales-Gonzalez A, Esquivel-Chirino C, et al. Inflammation, oxidative stress, and obesity. Int J Mol Sci 2011; 12(5): 3117-32.
  12. Calabrese V, Cornelius C, Leso V, Trovato-Salinaro A, Ventimiglia B, Cavallaro M, et al. Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes. Biochim Biophys Acta 2012; 1822(5): 729-36.
  13. Jain SK, Micinski D, Huning L, Kahlon G, Bass PF, Levine SN. Vitamin D and L-cysteine levels correlate positively with GSH and negatively with insulin resistance levels in the blood of type 2 diabetic patients. Eur J Clin Nutr 2014; 68(10): 1148-53.
  14. Chen SJ, Yen CH, Huang YC, Lee BJ, Hsia S, Lin PT. Relationships between inflammation, adiponectin, and oxidative stress in metabolic syndrome. PLoS One 2012; 7(9): e45693.
  15. Yokota T, Kinugawa S, Yamato M, Hirabayashi K, Suga T, Takada S, et al. Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with metabolic syndrome. Diabetes Care 2013; 36(5): 1341-6.
  16. Collazo-Roman M, Munoz-Forti K, Gonzalez A, Jimenez G, Mangual R, Perez Y, et al. Levels of antioxidant activity and oxidative stress in metabolic syndrome Puerto Rican participants (1138.9). The FASEB Journal 2014; 28(1_supplement): 1138-9.
  17. Thomas SR, Witting PK, Drummond GR. Redox control of endothelial function and dysfunction: Molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal 2008; 10(10): 1713-65.
  18. de Haan JB, Cooper ME. Targeted antioxidant therapies in hyperglycemia-mediated endothelial dysfunction. Front Biosci (Schol Ed) 2011; 3: 709-29.
  19. Yang ZH, Richard V, von SL, Bauer E, Stulz P, Turina M, et al. Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation 1990; 82(1): 188-95.
  20. Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol 1999; 61: 391-415.
  21. Touyz RM, Schiffrin EL. Role of endothelin in human hypertension. Can J Physiol Pharmacol 2003; 81(6): 533-41.
  22. Rossi R, Nuzzo A, Origliani G, Modena MG. Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women. J Am Coll Cardiol 2008; 51(10): 997-1002.
  23. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001; 285(19): 2486-97.
  24. Wendel A. Glutathione peroxidase. Methods Enzymol 1981; 77: 325-33.
  25. Bondonno CP, Yang X, Croft KD, Considine MJ, Ward NC, Rich L, et al. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: A randomized controlled trial. Free Radic Biol Med 2012; 52(1): 95-102.
  26. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Nitroglycerine-induced vasodilation for assessment of vascular function: A comparison with flow-mediated vasodilation. Arterioscler Thromb Vasc Biol 2013; 33(6): 1401-8.
  27. Samsamshariat SZA, Sakhaei F, Salehizadeh L, Keshvari M, Asgary S. Relationship between resistin, endothelin-1, and flow-mediated dilation in patient with and without metabolic syndrome. Adv Biomed Res 2019; 8: 16.
  28. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414(6865): 813-20.
  29. Maddux BA, See W, Lawrence JC Jr, Goldfine AL, Goldfine ID, Evans JL. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. Diabetes 2001; 50(2): 404-10.
  30. Kaneto H, Katakami N, Matsuhisa M, Matsuoka TA. Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Mediators Inflamm 2010; 2010: 453892.
  31. Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M. Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci U S A 1991; 88(22): 10045-8.
  32. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993; 91(6): 2546-51.
  33. Samsam-Shariat SZ, Bolhasani M, Sarrafzadegan N, Najafi S, Asgary S. Relationship between blood peroxidases activity and visfatin levels in metabolic syndrome patients. ARYA Atheroscler 2014; 10(4): 218-26.
  34. Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med 2011; 50(5): 567-75.
  35. Sies H. Glutathione and its role in cellular functions. Free Radic Biol Med 1999; 27(9-10): 916-21.
  36. Weiss N, Zhang YY, Heydrick S, Bierl C, Loscalzo J. Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction. Proc Natl Acad Sci U S A 2001; 98(22): 12503-8.
  37. Wiwanitkit V. Oxidative stress and metabolic syndrome. Korean J Fam Med 2014; 35(1): 44.
  38. Stephens JW, Gable DR, Hurel SJ, Miller GJ, Cooper JA, Humphries SE. Increased plasma markers of oxidative stress are associated with coronary heart disease in males with diabetes mellitus and with 10-year risk in a prospective sample of males. Clin Chem 2006; 52(3): 446-52.
  39. Vassalle C, Boni C, Di Cecco P, Landi P. Elevated hydroperoxide levels as a prognostic predictor of mortality in a cohort of patients with cardiovascular disease. Int J Cardiol 2006; 110(3): 415-6.
  40. Forsberg L, de Faire U, Morgenstern R. Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys 2001; 389(1): 84-93.
  41. Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L, et al. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 2003; 349(17): 1605-13.
  42. Sutipornpalangkul W, Morales NP, Charoencholvanich K, Harnroongroj T. Lipid
  43. peroxidation, glutathione, vitamin E, and antioxidant enzymes in synovial fluid from patients with osteoarthritis. Int J Rheum Dis 2009; 12(4): 324-8.
  44. Cardona F, Tunez I, Tasset I, Montilla P, Collantes E, Tinahones FJ. Fat overload aggravates oxidative stress in patients with the metabolic syndrome. Eur J Clin Invest 2008; 38(7): 510-5.
  45. Cardona F, Tunez I, Tasset I, Murri M, Tinahones FJ. Similar increase in oxidative stress after fat overload in persons with baseline hypertriglyceridemia with or without the metabolic syndrome. Clin Biochem 2008; 41(9): 701-5.
  46. Bougoulia M, Triantos A, Koliakos G. Plasma interleukin-6 levels, glutathione peroxidase and isoprostane in obese women before and after weight loss. Association with cardiovascular risk factors. Hormones (Athens) 2006; 5(3): 192-9.